Secondary Prevention Medical Therapy and Outcomes in Patients With Myocardial Infarction With Non-Obstructive Coronary Artery Disease.
- 作者列表："Paolisso P","Bergamaschi L","Saturi G","D'Angelo EC","Magnani I","Toniolo S","Stefanizzi A","Rinaldi A","Bartoli L","Angeli F","Donati F","Rucci P","Mattioli AV","Taglieri N","Pizzi C","Galiè N
Background:Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a heterogeneous entity with relevant long-term major cardiovascular events. Several trials have demonstrated that dual antiplatelet therapy (DAPT), β-blocker, renin-angiotensin-aldosterone system (RAAS) inhibitor and statin therapy improve the prognosis in patients with obstructive myocardial infarction (ob-MI). However, evidence on the best medical therapy for secondary prevention in MINOCA patients is lacking. Purpose:To investigate the effects of secondary prevention treatments at discharge on mid-term outcomes in MINOCA. Methods:Patients with acute myocardial infarction (MI) undergoing early coronary angiography between 2016 and 2018 were extracted from a clinical database. The diagnosis of MINOCA was made according to 2016 ESC MINOCA Position Paper criteria. Second-level diagnostic work-up including cardiac magnetic resonance was performed to exclude non-ischemic troponin elevation cause. The relationship between treatments and outcomes was evaluated by using Kaplan-Meier survival analysis and Cox regression models. All confirmed MINOCA were followed in our outpatient clinics. The primary end-points were all-cause mortality, re-hospitalization for MI and a composite outcome including all-cause mortality, hospitalization for MI and ischemic stroke (MACE). Results:Out of 1,141 AMI who underwent coronary angiography, 134 were initially diagnosed as MINOCA. Patients with MINOCA were less likely to receive secondary prevention treatments than patients with obstructive coronary artery disease (CAD) MI (respectively, 42.1% vs 81.8% for DAPT; 75.5% vs 89.6% for β-blockers; 64.7% vs 80.3% for RAAS inhibitor and 63.9% vs 83% for statins). Based on the diagnostic work-up completed during the first month after discharge, a final sample of 88 patients had confirmed MINOCA. During an average follow-up of 19.35 ± 10.65 months, all-cause mortality occurred in 11 (12.5%) patients, recurrence of MI in 4 (4.5%), and MACE in 15 (17.0%) patients. Patients treated with RAAS inhibitors and statins had a significantly longer survival. On the contrary, no increase in survival was found in patients treated with β-blockers or DAPT. Cox multivariable analysis, including all secondary prevention drugs, showed that only RAAS inhibitors were associated with reduced all cause-mortality and MACE. Conclusion:This prospective study suggests that RAAS inhibitor therapy provides mid-term beneficial effects on outcomes in MINOCA patients; in contrast, dual antiplatelet, β-blocker and statin therapy had no effects on mortality and MACE. These results should be considered preliminary and warrant confirmation from larger studies.
背景: 非阻塞性冠状动脉心肌梗死 (MINOCA) 是一种异质性实体，具有相关的长期主要心血管事件。多项试验表明，双联抗血小板治疗 (DAPT) 、 β 受体阻滞剂、肾素-血管紧张素-醛固酮系统 (RAAS) 抑制剂和他汀类药物治疗可改善阻塞性心肌梗死 (ob-MI) 患者的预后。然而，缺乏 MINOCA 患者二级预防的最佳药物治疗证据。 目的: 探讨出院时二级预防治疗对 MINOCA 中期结局的影响。 方法: 从临床数据库中提取 2018 和 2016年行早期冠状动脉造影的急性心肌梗死 (MI) 患者。根据 2016年 ESC MINOCA 位置纸标准诊断 MINOCA。进行包括心脏磁共振在内的二级诊断检查，以排除非缺血性肌钙蛋白升高原因。采用 Kaplan-Meier 生存分析和 Cox 回归模型评价治疗和结局之间的关系。我们门诊随访所有确诊的 MINOCA。主要终点是全因死亡率、 MI 再住院和复合结局，包括全因死亡率、 MI 住院和缺血性卒中 (MACE)。 结果: 在 1,141 例接受冠状动脉造影的 AMI 患者中，134 例初步诊断为 MINOCA。MINOCA 患者接受二级预防治疗的可能性低于阻塞性冠状动脉疾病 (CAD) MI 患者 (分别为 DAPT 42.1% vs 81.8%; β 受体阻滞剂 75.5% vs 89.6%; RAAS 抑制剂为 64.7% vs 80.3%，他汀类药物为 63.9% vs 83%)。根据出院后第一个月完成的诊断检查，88 例患者的最终样本确诊为 MINOCA。平均随访 19.35 ± 10.65 个月，全因死亡 11 例 (12.5%)，心肌梗死复发 4 例 (4.5%)，MACE 15 例 (17.0%) 病人。接受 RAAS 抑制剂和他汀类药物治疗的患者生存期显著延长。相反，在接受 β 受体阻滞剂或 DAPT 治疗的患者中，未发现生存率增加。Cox 多变量分析，包括所有二级预防药物，显示只有 RAAS 抑制剂与全因死亡率和 MACE 降低相关。 结论: 这项前瞻性研究表明，RAAS 抑制剂治疗对 MINOCA 患者的预后提供了中期有益的影响; 相比之下，双联抗血小板, β 受体阻滞剂和他汀类药物治疗对死亡率和 MACE 无影响。这些结果应被认为是初步的，需要从更大的研究中得到证实。
METHODS:BACKGROUND:People with stroke are not meeting recommended levels of physical activity. The modifiable factors associated with post-stroke physical activity levels need to be identified to develop targeted interventions. OBJECTIVE:The objective of this study was to investigate the factors at discharge from inpatient rehabilitation that are associated with physical activity levels at 3 months following discharge. DESIGN:This was a prospective cohort study. METHODS:Sixty-four people with stroke completed baseline assessments at discharge from inpatient rehabilitation and 55 completed the follow-up 3 months later. The candidate factors (i.e. gait speed, balance, strength, cognition, mood and motivation) were measured at discharge. The primary outcome measure at follow-up was walking related activity (measured by wrist-worn accelerometer). Secondary outcome measures were physical activity participation (Activity Card Sort) and intensity of physical activity (International Physical Activity Questionnaire - Short 7 days). Adjusted separate multivariable linear regression models or proportional odds regression models were used to evaluate the associations between candidate factors and physical activity. RESULTS:Gait speed and balance were associated with all aspects of physical activity. Higher level of intrinsic motivation was also associated with higher physical activity participation. Anxiety demonstrated a significant non-linear relationship with physical activity participation. LIMITATIONS:Inclusion of fatigue and individual muscle strength could have provided further insights into associations with steps per day. CONCLUSION:The results demonstrated that better physical function at discharge from inpatient rehabilitation was associated with future increased levels of physical activity. Additionally, higher levels of motivation impacted on increased physical activity participation. The influence of anxiety on physical activity participation requires further exploration. Mixed-method study designs can be utilized to further understand the factors associated with post-stroke physical activity.
METHODS:Cerebral ischemia-reperfusion (I/R) is characterized by initial transient cerebral ischemia followed by reperfusion. Various pathophysiological processes are involved in brain injury and functional recovery during cerebral I/R. There are few studies on dynamic metabolic process after cerebral I/R. The present study was to observe dynamic alteration of brain injury, functional recovery, and metabolites after cerebral I/R in rats and discover potential metabolic markers. The cerebral I/R model was established by middle cerebral artery occlusion (MCAO) for 90 min, following reperfusion in rats. The results of cerebral infarction area, cerebral edema, and behavior test showed that there were dynamic changes in brain injury and functional recovery at different periods after cerebral I/R. Further analysis showed that the brain injury was severe on the first day of cerebral I/R, and there was a significant functional recovery from the 7th day of cerebral I/R, followed by an aggravation trend of brain injury from the days 7 to 28. Furthermore, Matrix-assisted laser desorption ionization mass spectrometry imaging analysis showed that the expression of ATP, glucose, and citric acid on 7th day was the highest during cerebral I/R, which indicated that energy metabolism and oxidative phosphorylation played important roles during cerebral I/R. In addition, the untargeted metabolomic results showed that the level of isocitric acid, the ratio of oxyglutaric acid/glutamic acid, and the level of pyruvic acid associated with the TCA cycle were also the highest on the 7th day during cerebral I/R, which indicated that the transient spontaneous recovery of ischemic brain on the 7th day after ischemia-reperfusion might be related to oxidative phosphorylation and energy metabolism in the brain in this period. In conclusion, the results suggest that some small molecule metabolites participate in the brain injury and functional recovery during cerebral I/R, which is of great significance to the development of therapeutic drugs and diagnostic markers.
METHODS:The aims of this study were to study the effects of miR-2 on cerebral ischemia–reperfusion rats and to explore its further mechanism. Rats were assigned into sham, model, miR-22 control and miR-22 groups. Observation of neurological behaviors at 24 h after operation found that neurological functions were severely damaged in the model and miR-22 control groups and these damages were improved by miR-22. RT-PCR indicated that miR-22 mRNA level in the brain tissue was significantly decreased in the model and miR-22 control groups, but increased in the miR-22 group. TTC staining showed increased percentage of cerebral infarction volume in the model and miR-22 control groups and this increase was reduced by miR-22. Immunohistochemistry showed increased densities of CD34^+ and VEGF^+ microvessels in the cortex in the model and miR-22 control groups, which were further increased in the miR-22 group. ELISA showed increased serum VEGF and Ang-1 levels in the model and miR-22 control groups, which were also further increased in the miR-22 group. Western blot analysis showed increased phosphorylation level of PI3K and Akt in brain tissue in the model and miR-22 control groups, which were further increased in the miR-22 group. Administration of LY294002, a specific PI3K pathway inhibitor, significantly reversed all the effects of miR-22 on rats in the model group. miR-22 exerts its neuroprotective and angiogenic functions via the PI3K/Akt signaling pathway, at least partly, in rats under cerebral ischemia–reperfusion.